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Minas Gerais is a Brazilian state known as the largest cheese producer in Brazil. Minas Artisanal Cheese (MAC) is produced in different regions of this Brazilian state using raw cow milk to which a natural starter culture ("pingo") is added. "Entre Serras" is one of these regions, in which the MAC production had decreased (even stopped) for decades until recently, when artisanal cheeses production has been resurrected. Here, we aimed to gain insights on the bacterial diversity of "Entre Serras" MAC. 16S rRNA gene amplicon sequencing was used to assess the bacterial community in cheeses produced by four farms (A, B, C, and D) over 60 days of ripening. Overall, Lactococcus lactis was the predominant species found, regardless of the producer/farm. Enterococcus, Streptococcus, Lactobacillus and Leuconostoc genera were also prevalent in the samples microbiota and their levels varied according to the producer/farm. Cheeses produced by Farms A and B presented high contaminant levels (mainly Enterobacteriaceae and S. aureus), which may be attributed to poor hygiene during cheese production and/or herd health management. Chao1 indices varied significantly when the estimated species richness values of the producers/farms were compared (p less then 0.05). A principal coordinate analysis also revealed distinct microbial communities for some farms (p less then 0.001). However, no statistical significance was identified when samples were grouped by ripening time. https://www.selleckchem.com/products/fhd-609.html Core microbiota analysis indicated that "Entre Serras" MAC microbiota includes not only LAB, but also spoilage and potentially pathogenic bacteria. We provide the first insights on the bacterial diversity of "Entre Serras" MAC, helping the understanding of the inter-regional microbiological diversity of the samples.Inflammatory bowel diseases (IBDs), mainly Crohn's disease and ulcerative colitis, are high-prevalent chronic gastrointestinal disorders that may cause an important reduction in life quality. Such diseases are characterized by their immune-mediated inflammatory, oxidative and dysbiotic events, which can lead to important symptoms in patients, such as abdominal pain, bloody diarrhea and body weicght loss. In the last years, alternative natural options have been postulated for the prevention or treatment of IBDs, since common drug therapy may not be well accepted due to recurrent adverse effects and/or partial efficacy. Among those new natural products, agro-industrial byproducts, such as the peel and seed of foods, are emerging as cheap and pro-ecological options, as they are rich in bioactive compounds, such as polyphenols, but also in non-phenolic compounds, like unsaturated fatty acids, dietary fibers and prebiotics, carotenoids, bioactive peptides, and vitamins. In that sense, Latin America is rich in little explored native fruits and vegetables, from which great amounts of byproducts can be produced. Studies have shown that the byproducts from Latin American vegetables, such as passion-fruit (Passiflora edulis), pineapple (Ananas comosus) and pumpkin (Cucurbita spp.), for example, could represent interesting tools against IBDs, judging by the results of in vitro and animal studies. Therefore, the aim of this review is to discuss the potential role of non-phenolic compounds from native Latin American food byproducts in the prevention or treatment of IBDs, by highlighting their anti-inflammatory, anti-oxidative and/or anti-dysbiotic effects.Phenyllactic acid (PLA) as a phenolic acid by lactic acid (LA) bacteria shows enhanced antibacterial activity when coexisting with LA, while the antibacterial mechanism of PLA combined with LA was unknown. Hence, the antibacterial mechanism of PLA and LA was investigated against Bacillus cereus. Flow cytometry and TEM analysis demonstrated that single PLA and LA disrupted the membrane integrity and the morphology, while combined PLA and LA synergistically enhanced the damage. iTRAQ-based proteomic analysis suggested that PLA down-regulated kdpB and inhibited K+ transport, disturbed the function of ribosome and expression of competence genes; LA down-regulated periplasmic phosphorus-binding proteins and inhibited phosphorus transport, disturbed the function of ribosome, TCA cycle, as well as purine and pyrimidine metabolism; and combined PLA and LA inhibited K+ and phosphorus transport, and influenced the synthesis of purine and pyrimidine metabolism. The investigation could provide some insights into the application of PLA in food preservation.Mutations in the group of epigenetic modifiers are the largest group of mutated genes in Myelodysplastic Syndromes (MDS) and are very frequently found in Acute Myeloid Leukemia (AML). Our advancements in the understanding of epigenetics in these diseases have helped develop groundbreaking therapeutics that have changed the treatment landscape of MDS and AML, significantly improving outcomes. In this review we describe the most common epigenetic aberrations in MDS and AML, and current treatments that target mutations in epigenetic modifiers, as well as novel treatment combinations, from standard therapies to investigational treatments.The DNA methyltransferase inhibitor azacytidine (aza) may reactivate pathways associated with plasma cell differentiation, cell cycle control, apoptosis, and immune recognition and thereby restore sensitivity to lenalidomide (len) and dexamethasone (dex) in relapsed and/or refractory multiple myeloma (RRMM). We aimed to develop an aza regimen that reaches epigenetically active levels 8 times in 28 days with less bone marrow toxicity than the myeloid malignancy standard of 7 consecutive doses to enable safe combination with len. Aza was escalated from 30 mg/m2 once a week up to a predefined maximum of 50 mg/m2 twice a week in combination with GFR-adjusted len (≥ 60 mL/min 25 mg, 3059 mL/min 10 mg) day 1 to 21 every 28 days and dex 40 mg once a week followed by a limited expansion study to a total N of 23 at the highest tolerated dose. Fifty-one patients (pts) with RRMM were screened, 42 were treated and 41 were evaluable for response based on at least 1 response assessment or progression after treatment start.
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